Topic 3 Amino Acid and Protein-edited

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Protein Degradation in the Human DigestiveProtein Degradation in the Human DigestiveTract Tract



22

Digestion of ProteinsStomach: Pepsinogen Pepsin (max. act. pH 2)

Small Intestine: Trypsinogen Trypsin

Trypsin cleaves:

Chymotrypsinogen to chymotrypsinProelastase to elastase

Procarboxypeptidase to carboxypeptidase

Aminopeptidases (from intestinal epithelia)

Enteropeptidase



33

Dynamics of Protein

And Amino Acid Metabolism

Dietary Proteins Digestion to Amino Acids

Transport in Blood to Cells

Protein Synthesis Functional Proteins

Protein Degradation In

Proteasomes Following

Tagging With Ubiquitin

Amino Acids

Metabolites



A mino acid pool A mino acid pool

No storage facility for aminoNo storage facility for amino

acidsacids

A mino acids incorporated into

A mino acids incorporated intofunctional proteinsfunctional proteins

A mino acids in blood and A mino acids in blood and

extracellular fluid represent anextracellular fluid represent an

amino acid pool amino acid pool

A mino acids move through this A mino acids move through this

poolpool

A verage 60 kg woman A verage 60 kg woman

10 kg protein10 kg protein

170 g free amino acids in pool170 g free amino acids in pool

From: Summerlin LR (1981) Chemistry for the Life Sciences.New York: Random House p 563.



55

Lumen

Amino Acids Oligopeptides

Intestinal Absorption

Oligopeptides

Amino Acids

Peptidase

s

Blood

Transport

Protein



A mino acid metabolism A mino acid metabolism

Metabolism of amino acids differs, but 3Metabolism of amino acids differs, but 3

common reactions:common reactions:

TransaminationTransamination

DeaminationDeamination

Formation of ureaFormation of urea



Transamination reactionsTransamination reactions

A mino group removed from one A mino group removed from oneamino acid and transferred toamino acid and transferred toanotheranother

Catalysed by aminotransferaseCatalysed by aminotransferaseenzymesenzymes

Nearly all transaminations transferNearly all transaminations transferamino group toamino group to EE--ketoglutarateketoglutarate Forms new ketoacid and glutamateForms new ketoacid and glutamate

(amino acid)(amino acid)

BC AA transaminations in SMBC AA transaminations in SMusually result in formation of usually result in formation of alanine (via glutamate)alanine (via glutamate) Released from muscleReleased from muscle

A llows amino groups from BC AA s A llows amino groups from BC AA sto move from SM to liver forto move from SM to liver for

disposaldisposal

From: Houston, ME. (2001) Biochemistry Primer for ExerciseScience. Champaign: Human Kinetics. p151



88

TransaminationsTransaminationsGlutamate E-Ketoglutarate

+ +

Pyruvate Alanine

Glutamate E-Ketoglutarate

+ +

Oxaloacetate Aspartate

Glutamate-Pyruvate

Aminotransferase

(Alanine Transferase ALT)

Glutamate-Oxaloacetate

Aminotransferase

(Aspartate Transferase AST)



Deamination reactionsDeamination reactions

A mino group (and H) A mino group (and H)removedremoved

Forms ammonia (NHForms ammonia (NH33)) Carbon skeleton left Carbon skeleton left can becan be Oxidised in KCOxidised in KC

used forused for

gluconeogenesisgluconeogenesis converted to fatty acidconverted to fatty acid

18 amino acids18 amino acidsglucogenic/ketogenicglucogenic/ketogenic Leucine and lysineLeucine and lysine

purely ketogenicpurely ketogenic

From: Houston, ME. (2001) Biochemistry Primer for Exercise Science.Champaign: Human Kinetics. p148



DeaminationDeamination is also an oxidative reaction that occursis also an oxidative reaction that occursunder aerobic conditions in all tissues but especiallyunder aerobic conditions in all tissues but especiallythe liver.the liver.

DuringDuring oxidativeoxidative deaminationdeamination, an amino acid is, an amino acid isconverted into the correspondingconverted into the corresponding ketoketo acid by theacid by theremoval of the amine functional group as ammoniaremoval of the amine functional group as ammonia

and the amine functional group is replaced by theand the amine functional group is replaced by theketoneketone group.group.

The ammonia eventually goes into the urea cycle.The ammonia eventually goes into the urea cycle.

OxidativeOxidative deaminationdeamination occurs primarily onoccurs primarily on glutamicglutamicacid becauseacid because glutamicglutamic acid was the end product of acid was the end product of

manymany transaminationtransamination reactions.reactions. EnzymeEnzyme -- glutamateglutamate dehydrogenasedehydrogenase



Oxidative DeaminationOxidative Deamination

Glutamate formed by transamination reactionsGlutamate formed by transamination reactionsis deaminated tois deaminated to EE--ketoglutarateketoglutarate

Glutamate dehydrogenaseGlutamate dehydrogenase -- N A DN A D++ or N A DPor N A DP++ isiscoenzymecoenzyme

Other AA oxidasesOther AA oxidases -- (liver, kidney) low activity(liver, kidney) low activity







Urea cycleUrea cycle

A mmonia is toxic A mmonia is toxic

Readily ionises toReadily ionises to

ammonium ion NHammonium ion NH44++

NHNH44++ converted to ureaconverted to urea

in liver (urea cycle)in liver (urea cycle)

U

rea contains 2 x NHU

rea contains 2 x NH22

One from NHOne from NH44++

One fromOne from

aspartateaspartate

Urea excreted in urineUrea excreted in urine

From: Stryer, LS (1988) Biochemistry (3rd Ed). New York: WH Freeman& Co. p500



Transport and detoxication of ammoniaTransport and detoxication of ammonia

A mmonia has to A mmonia has tobe transported tobe transported toliverliver

Glutamine is theGlutamine is the

major transport major transport formform

Glutamine servesGlutamine servesas a source of as a source of amine groups foramine groups forbiosynthesis.biosynthesis.



Synthesis of ureaSynthesis of urea

LiverLiver 55--step Urea Cycle (Small Krebs c., Krebsstep Urea Cycle (Small Krebs c., Krebs--

Hensleit c., Ornitihin c.)Hensleit c., Ornitihin c.)

Uses ammonia, COUses ammonia, CO22, 3 A TP and aspartate, 3 A TP and aspartate



Interconnection of the urea cycle with thecitrate cycle





Metabolism of amino nitrogen



Roles of ProteinRoles of Protein

bulk compositionbulk composition of the body (structuralof the body (structuralaspects of the cell)aspects of the cell)

oxidative metabolismoxidative metabolism (used as energy(used as energysource in energysource in energy--deficient diets)deficient diets)

enzymesenzymes (globular proteins that regulate(globular proteins that regulateand influence metabolism)and influence metabolism)

plasma proteinsplasma proteins (circulating, mobile(circulating, mobileproteins such as immune bodies)proteins such as immune bodies)

hormoneshormones (regulatory role)(regulatory role)



Special FunctionsSpecial Functions

peptidespeptides (formation of proteins)(formation of proteins)

purines/pyrimidinespurines/pyrimidines (control of protein(control of proteinsynthesis)synthesis)

histamineshistamines (active compounds, allergies)(active compounds, allergies)

conjugated proteinsconjugated proteins (assist in the excretion(assist in the excretionof other compounds)of other compounds)

pigmentspigments (e.g., melanin, derived from(e.g., melanin, derived fromamino acids)amino acids)



Classification Based on ChemicalConstitution

Small amino acids Glycine, A lanine

Branched amino acids Valine, Leucine, Isoleucine

Hydroxy amino acids (-OH group) Serine, Threonine

Sulfur amino acids Cysteine, Methionine

Aromatic amino acids Phenylalanine, Tyrosine, Tryptophan

Acidic amino acids and their derivatives A spartate,

A sparagine, Glutamate, Glutamine

Basic amino acids Lysine, A rginine, Histidine

Imino acid - Proline



Required in dietRequired in diet

Humans incapable of forming requisiteHumans incapable of forming requisite

carbon skeletoncarbon skeleton

Arginine*

Histidine*

Isoleucine

LeucineValine

Lysine

Methionine

Threonine

PhenylalanineTryptophan

* Essential in children, not in adults

Essential Amino Acids in Humans



Not required in dietNot required in diet

Can be formed from aCan be formed from a--keto acids byketo acids by

transamination and subsequenttransamination and subsequent reactionsreactions

Alanine

Asparagine

Aspartate

GlutamateGlutamine

Glycine

Proline

Serine

Cysteine (from Met*)Tyrosine (from Phe*)

* Essential amino acids

Non-Essential Amino Acids in Humans



Major Functions of Amino Acids Derived Major Functions of Amino Acids Derived

from Dietary Proteinfrom Dietary Protein

OxidationOxidationGlycogenic amino acids:Glycogenic amino acids: ----Blood glucoseBlood glucose----EnergyEnergy

KetogenicKetogenic amino acids:amino acids: --Acetyl Acetyl CoACoA--StoredStored fatfat--EnergyEnergy

Biosynthesis of nitrogenBiosynthesis of nitrogen--containing metabolitescontaining metabolites

Heme Blood cell

Choline Physiological-signaling,

neurotransmission

Glycosamine Sugar

Nucleotides DNA

Protein synthesis Protein

Biogenic amines Neurotransmitters

Carnitine Heart

Creatine phosphate « Energy »



ProteinsProteins A mino A cid: Basic building block of protein A mino A cid: Basic building block of protein

Contain at least one amine (NHContain at least one amine (NH22) and one) and onecarboxyl group (COOH).carboxyl group (COOH).

Difference lies in their side chain.Difference lies in their side chain.

A mino A cids are joined by peptide bonds A mino A cids are joined by peptide bonds

Two AA = DipeptidetripeptidepolypeptideTwo AA = Dipeptidetripeptidepolypeptide

Polypeptides can be in several different Polypeptides can be in several different arrangements. A K A structural proteins.arrangements. A K A structural proteins.

A single cell contains thousands of A single cell contains thousands of different protein molecules.different protein molecules.



Fig 13.3 The four levels of organization in proteins.Fig 13.3 The four levels of organization in proteins.



All All the amino acids exceptthe amino acids except prolineprolinecontain a free amino group and a freecontain a free amino group and a free

carboxyl group.carboxyl group.



ProteinsProteins

20 Different AAs required by20 Different AAs required bybody (Found in plants & animals)body (Found in plants & animals)

Essential : (8) Can not beEssential : (8) Can not besynthesizedsynthesized

NonNon--Essential : (12) Can beEssential : (12) Can bemanufactured by the bodymanufactured by the body



ProteinsProteins

IngestedIngested

Plant vs A nimal: Neither is superiorPlant vs A nimal: Neither is superior

Synthesized by BodySynthesized by Body

TransaminationTransamination

Synthesis of AA s from carbon, oxygen,Synthesis of AA s from carbon, oxygen,& hydrogen fragments of carbs & lipids.& hydrogen fragments of carbs & lipids.

Often times simply transfer of amineOften times simply transfer of aminegroupgroup



ProteinsProteins

DeaminationDeamination

Amino group is removed from AA. Amino group is removed from AA.

Remaining carbon skeleton can then beRemaining carbon skeleton can then be

converted to carbohydrate or lipid.converted to carbohydrate or lipid.Remaining amino group forms urea inRemaining amino group forms urea in

liver and is excreted by kidneys.liver and is excreted by kidneys.

Approximately 100 g of protein is Approximately 100 g of protein isbroken down and rebuilt every day.broken down and rebuilt every day.

80 g80 g pp urine , 20 gurine , 20 g pp feces & sweatfeces & sweat



T he Stereochemistry of Amino Acids

Chiral molecules existing in two forms

http://www.imb-jena.de/~rake/Bioinformatics_WEB/gifs/amino_acids_chiral.gif



The two stereoisomers of alanine

Ecarbon is a chiral center

Two stereoisomers are

called enantiomers.

The solid wedge-shaped bondsproject out of the plane of paper, the dashed bonds

behind it.

The horizontal bonds project out of the plane of paper, thevertical bonds behind.



DN A mRN A protein



Recommended IntakeRecommended Intake

Recommended intake increasesRecommended intake increasesSLIGHTLYSLIGHTLY with stress, disease,with stress, disease,

injury, prolonged heat exposure, andinjury, prolonged heat exposure, andintense strength training.intense strength training.

Increased protein needs for athletesIncreased protein needs for athletesare usually met by the increasedare usually met by the increasedprotein intake as result of increasedprotein intake as result of increased

caloric intake.caloric intake.



Excess ProteinExcess Protein

Will not increase muscle mass orWill not increase muscle mass orprotein stores in body.protein stores in body.

ALL ALL excess protein is deaminatedexcess protein is deaminatedand used as energy or stored asand used as energy or stored as

F A T.F A T.

Very taxing on liver and kidneys!! Very taxing on liver and kidneys!!

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Topic 3 Amino Acid and Protein-edited